Apheresis: Process of collecting one or more components by mechanized processing of whole blood during which the non-collected components are returned to the donor during or at the end of the process.

Blood collection: The process of collecting blood for eventual transfusion purposes from Human Donors.

Blood components: A therapeutic constituent of blood (red cells, plasma, white cells, platelets, cryoprecipitate) that can be prepared various methods.

Blood establishment: Any entity that performs or is responsible for any activity from the collection, testing, processing, storage and distribution of human blood/blood components when intended for transfusion. This does not include Hospital Blood Bank.

Calibration: Set of operations that establish, under specified conditions, the relationship between values indicated by a measuring instrument/system or values represented by a material measure and the corresponding known values of a reference standard.

Change control: A formal system by which qualified representatives of appropriate disciplines review proposed or actual changes that might affect the validated status of facilities, systems, equipment or processes. The intent is to determine the need for action that would ensure and document that the system is maintained in a validated state.

Closed system:  A system in which the contents are not exposed to air or outside elements during the collection, preparation and separation of components. 

Computerized system: A system comprising the input of data, electronic processing and the output of information to be used either for reporting, automatic control or documentation. 

Contract acceptor: The facility that performs specified work/services under a documented contract for a different institution.

Contract giver: The facility that subcontracts specific work/services to a different institution and is responsible for setting up a contract defining roles and responsibilities of each side.

Distribution: Act of delivery of blood and blood components to other blood establishments, hospital blood banks, and manufacturers of blood- and plasma-derived products. It does not include issuing blood or blood components for transfusion.

Donor deferral: The temporary or permanent suspension of a potential donor to donate blood

Donor: A person in normal health with a good medical history who voluntarily gives blood or blood components for therapeutic use.

Fractionation: The process of obtaining specific products from Plasma through various steps and processes.

GMP Good Manufacturing Practice: All elements in established practice that collectively lead to final products which consistently meet pre-defined specifications and compliance with defined standards and regulations.

Good Practice: All elements in established practice that collectively lead to final blood or blood components that consistently meet pre-defined specifications and compliance with defined regulations.

Hospital Blood Bank: Any entity, which stores, performs compatibility testing and issues human blood or blood components for transfusion exclusively for use within the hospital/institution facilities.

Mobile site: A temporary or movable place used for the collection of blood and blood components which is in a location outside of, but under the control of the blood establishment.

NAT Test (Nucleic Acid Amplification Test): This is a testing (analytical) system utilized to detect specific DNA/RNA.

National regulatory authority: The National Authority responsible for Licensing/authorising specific institutions to perform specific activities and to set appropriate standards.

Non-conformance: The nonfulfillment in a process, procedure or product of a specified requirement.

Open system: A system in which a breach has occurred but every effort is made to prevent   microbiological contamination by operating in a clean environment using sterilized materials and aseptic handling techniques.

Procedure: A procedure controls a distinct process or activity, including the associated inputs and outputs. A series of tasks usually performed by one person according to instructions.

Process: A set of related tasks and activities that accomplish a work goal. 

Processing: Any step in the preparation of a blood component that is carried out between the collection of blood and the issuing of a blood component.

Qualification: Part of Validation which verifies that any equipment, personnel or premises functions correctly and delivers the expected outcomes.

Quality assurance: a wide concept that covers all aspects that collectively or individually impact the quality of the product. It is a good practice in the manufacture of blood and blood products, as it is the process of vouching for integrity of products to meet the standard for the proposed use.

Quality Control: the part of GMP which involves sampling, specifications and testing as well as with the organization, documentation and release procedures which ensure that materials are not released for use in critical processes and blood components are not released for distribution unless predefined critical parameters have been assessed and items found compliant.

Quality management: The coordinated activities to direct and control an organization with regard to quality at all levels within the blood establishment. 

Quality Monitoring: That part of a quality assurance program concerned with maintenance and improvement of quality which deals with the identification and use of indicators to detect variations from standards or specifications.

Quality System: The organizational structure, responsibilities, procedures, processes, and resources for implementing quality management.

Quarantine: The physical isolation of blood components or incoming materials/reagents over a variable period of time while awaiting acceptance, issuance or rejection of the blood.

Record: Written or electronically captured evidence that an event has occurred or an outcome has been achieved. A document that contains objective evidence which shows how well activities are being performed or what kind or results are being achieved.

Responsible Person “Authorized Person”: The Responsible Person(s) should ensure that every unit of blood or blood component has been collected, tested, processed, stored, and distributed in compliance with the laws in force in that country and (if applicable) with the requirements of the Marketing Authorization. The Responsible Person(s) shall meet the qualification requirements laid down in the national legislation, they shall be permanently and continuously at the disposal of the blood establishment to carry out their responsibilities.  

Risk assessment: Method to assess and characterize the critical parameters in the functionality of equipment, systems or processes. 

Standard Operating Procedures (SOP): Detailed written procedures that give direction for performing certain operations.

Statistical process control (SPC): use of statistical techniques to control a process or production method. SPC tools and procedures can help you monitor process behavior, discover issues in internal systems, and find solutions for production issues.

Validation: The establishment of documented and objective evidence that the predefined requirements of a process/procedure are consistently fulfilled.​

1.1. General requirements 

1.1.1 Each blood establishment must develop and maintain a Quality System that is based on the principles of Good Manufacturing Practices GMP.

1.1.2 For blood and blood components imported from countries outside Saudi Arabia and intended for use or distribution in Saudi Arabia, there must be a Quality Management System for blood establishments in the stages preceding importation equivalent to the Quality Management System established in Saudi Arabia.

1.1.3 Quality must be recognised as being the responsibility of all persons involved in the processes of the blood establishment and Hospital Blood Banks, with management ensuring a systematic approach towards quality and the implementation and maintenance of a Quality Management System

1.1.4 Attainment of this quality objective is the responsibility of executive management. It requires the participation and commitment both of staff in many different departments and at all levels within the organization and of the organization’s suppliers and distributors. To achieve this quality objective reliably there must be a comprehensively designed and correctly implemented Quality Management System incorporating Good Practice and Quality Risk Management.

1.1.5 Each actor in the supply chain should establish, document, and fully implement a comprehensively designed Quality Management System to deliver Quality Assurance based on the principles of Quality Risk management by incorporating Good Practice and Quality Control.

1.1.6 The basic concepts of Quality Management, Good Practice and Quality Risk Management are inter-related. They are described here in order to emphasize their relationships and fundamental importance to the preparation of blood and blood components.

1.2 Quality Management System

1.2.1 Quality Management is a wide-ranging concept covering all matters, which individually or collectively influence the quality of blood and blood components. It is the sum total of the organized arrangements made with the objective of ensuring that blood components are of the quality required for their intended use. Quality Management therefore incorporates Good Practice.

1.2.2 The Quality Management System encompasses quality management, quality assurance, continuous quality improvement, personnel, premises and equipment, documentation, collection, testing and processing, storage, distribution, quality control, blood component recall, and external and internal auditing, contract management, non-conformance and self- inspection.

1.2.3 The Quality Management System shall ensure that all critical processes are specified in appropriate instructions and are carried out in accordance with the standards and specifications of the current Good Practice and comply with appropriate National regulations.

1.2.4 The Quality Management System must be designed to assure the quality and safety of prepared blood and blood components, as well as ensure donor and staff safety and customer service. This strategy requires the development of clear policies, objectives and responsibilities. It also requires implementation by means of quality planning, quality control, quality assurance and quality improvement to ensure the quality and safety of blood and blood components, and to provide customer satisfaction.

1.2.5 Top Management has the ultimate responsibility to ensure that an effective Quality Management System is in place and resourced adequately, and that roles and responsibilities, are defined, communicated and implemented throughout the organization. Executive management’s leadership and active participation in the Quality Management System is essential. This leadership should ensure the support and commitment of staff at all levels and sites within the organization to the Quality Management System.

1.2.6 Executive management should establish a quality policy that describes the overall intentions and direction of the blood establishment and/or hospital blood bank (herein after referred to as ‘organization’) related to quality. They should also ensure Quality Management System and Good Practice governance through management review to ensure its continuing suitability and effectiveness.

1.2.7 The Quality Management System should be defined and documented. A Quality Manual or equivalent document should be established and contain a description of the Quality Management System (including management responsibilities).

1.2.8 The Quality Management System documentation shall include: Statements of a quality policy and quality objectives, quality manual, documented procedures and records required by Good Manufacture Practice, documents, including records, determined by the organization to be necessary to ensure the effective planning, operation, and control of its processes and other documentation specified by applicable regulatory requirements.

1.2.9 All blood establishments and hospital blood banks must be supported by a quality assurance function (whether internal or related) for fulfilling quality assurance. That function must be involved in all quality-related matters, and must review and approve all appropriate quality- related documents.

 1.2.10. An independent function with responsibility for quality assurance should be established. This quality assurance function will be responsible for the oversight of all quality processes but need not necessarily be responsible for carrying out the activities. 

1.2.11. All procedures, premises and equipment that have an influence on the quality and safety of blood and blood components should be validated and qualified before introduction and should be re-validated and re-qualified at regular intervals, as determined as a result of these activities. 

1.2.12. A general policy regarding qualification of facilities and equipment as well as validation of processes, automated systems and laboratory tests should be in place. The formal objective of qualification and validation is to ensure compliance with the intended use and regulatory requirements. 

1.2.13. A formal change control system should be in place to plan, evaluate and document all changes that may affect the quality, traceability, availability or effect of components, or the safety of components, donors or patients. The potential impact of the proposed change should be evaluated, and the degree of revalidation or additional testing, qualification and validation needed should be determined. 

1.2.14. A formal system for the handling of deviations and non-conformances should be in place. An appropriate level of root-cause analysis should be applied during the investigation of deviations, suspected product defects, and other problems. This strategy can be determined using Quality Risk Management principles. If the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing them. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system-based errors or problems have not been overlooked, if present. Appropriate corrective actions and/or preventive actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed in accordance with Quality Risk Management principles. 

1.2.15. Management should review the system at regular intervals to verify its effectiveness and introduce corrective measures if deemed necessary. 

There should be periodic management review and monitoring both of its effectiveness, with the involvement of senior management and of the operation of the Quality System to identify opportunities for continual improvement of blood and blood components processes and the system itself.

Product quality reviews should be conducted with the objective of verifying the consistency of the existing process and the appropriateness of current specifications in order to highlight trends and to identify improvements in both component and process. 

A product quality review may also be considered as an instrument for surveying the overall quality status of a blood component and its manufacturing processes, including the collection. Such a review should normally be conducted annually and should be documented. It may include: 

            Review of starting materials; 

            Review of critical in-process controls; 

            Review of results of quality control and quality monitoring; 

            Review of all changes; 

            Review of the qualification status of equipment; 

            Review of technical agreements and contracts; 

            Review of all significant deviations, non-conformances, and the corrective actions implemented; 

            Review of the findings of internal and external audits and inspections, and the corrective actions implemented;

            Review of complaints and recalls; 

            Review of donor acceptance criteria; 

            Review of donor deferrals; 

            Review of look-back cases.

1.3. Good practice 

    Good Practice is the part of Quality Management that ensures that blood and blood components are produced and controlled consistently to the quality standards appropriate to their intended use. Good Practice is concerned with collection, processing, testing, release and storage (hereinafter included in the generic term ‘preparation’) and quality control. The basic requirements are: 

1.3.1 All processes are defined clearly and reviewed systematically in the light of experience and shown to be capable of consistently delivering blood and blood components of the required quality and complying with their specifications. This strategy includes ensuring that: 

1.3.1.1. critical steps and significant changes to the process are validated; 

1.3.1.2. all requirements are provided including: 

            Appropriately qualified and trained personnel; 

            Adequate premises and space; 

            Suitable equipment and services; 

            Correct materials, containers and labels;

            Approved procedures and instructions; 

            Suitable storage and transport; 

            Instructions and procedures are written in an instructional form in clear and unambiguous language, and are applicable specifically to the facilities provided; 

            Operators are trained to carry out procedures correctly; 

            Records are made, manually and/or by recording instruments, during preparation which demonstrate that all the steps required by the defined procedures and instructions were in fact taken and that the quantity and quality of the blood or blood component was as expected; 

1.3.1.3. any significant deviations are fully recorded and investigated; 

1.3.1.4. records of preparation (including distribution) that enable the complete history of the blood or blood component to be traced are retained in a comprehensible and accessible form; 

1.3.1.5. the distribution of the blood and blood components minimizes any risk to their quality; 

1.3.1.6. a system is available to recall any blood or blood component (including those prepared using a batch of critical materials that have been distributed or issued);

1.3.1.7. Complaints about blood and blood components are examined, the causes of quality defects investigated, and appropriate measures taken in respect of the defective blood components to prevent reoccurrence. 

1.3.2. Quality Control is the part of Good Practice that is concerned with sampling, specifications and testing, as well as with the organization, documentation and release procedures which ensure that materials are not released for use in preparation, and blood and blood components are not released for distribution, until their quality has been judged to be satisfactory and that the necessary and relevant tests have been carried out. The basic requirements are: 

1.3.2.1. Adequate facilities, trained personnel and approved procedures are available for sampling, inspecting/testing starting materials, packaging materials, intermediate components, and finished blood and blood components and, if appropriate, for monitoring environmental conditions;

    1.3.2.2. Samples of starting materials, packaging materials, intermediate, and finished    blood components are taken by approved personnel and methods;

1.3.2.3. Test methods are validated;

1.3.2.4. Records are made, manually and/or by recording instruments, which demonstrate   that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are recorded and investigated fully;

1.3.2.5. The finished blood and blood components comply with the specifications and are correctly labelled;

1.3.2.6. Records are made of the results of inspection, and that testing of materials, intermediate and finished blood and blood components are formally assessed against specifications;

1.3.2.7. No blood or blood components are released for distribution that do not comply with the requirements of the relevant authorizations.

1.3.3. Rolling quality reviews of all blood and blood components should be conducted with the objective of continuously verifying: the consistency of the existing process; appropriateness of current specifications for both starting materials and finished blood components to highlight any trends and to identify product and process improvements. 

1.3.4 All quality control procedures must be validated before use.

1.3.5 Results of quality-control testing must be evaluated continuously and steps taken to correct defective procedures or equipment. Standard procedures for the quality control of blood components must be in place. The suitability of each analytical method to provide the intended information must be validated.

1.3.6 Quality control of blood and blood components must be carried out according to a sampling plan designed to provide the intended information.

Testing must be done in accordance with the instructions recommended by the manufacturer of the reagents and/or test kits and approved by SFDA.

The performance of the testing procedures must be regularly assessed by participation in a formal system of proficiency testing (external QC).

Records of quality-control procedures must include identification of the person(s) undertaking the tests or procedures. Any corrective action taken must also be recorded. If corrections in record are necessary, the original recording must not be obliterated, but must remain legible.

1.4. Quality risk management 

Quality Risk Management is the part of the Quality System that ensures that the process performance and quality monitoring and review systems are based on the principles of risk management. Appropriate statistical tools should be used (where appropriate) in the assessment of ongoing process capability. 

1.4.1 The Quality System should ensure that all critical processes are specified in appropriate instructions and are carried out in accordance with the standards and specifications of Good Practice and comply with appropriate regulations. These processes should incorporate the principles of Quality Risk Management and systematically ensure that: 

1.4.2 The evaluation of the risk to quality is based on scientific knowledge, experience with the process and, ultimately, is connected to protection of the donor, patient and staff; 

1.4.3 The level of effort, formality and documentation of the quality risk management process is commensurate with the level of risk.

1.5. Deviation management and corrective and preventive actions

1.5.1 A system to ensure corrective and preventive actions for blood component nonconformity and quality problems must be in place.

1.5.2 Data must be routinely analyzed to identify quality problems that may require corrective action or to identify unfavorable trends that may require preventive action

1.5.3 All errors and accidents must be documented and investigated in order to identify problems for correction.

1.5.4 Deviations with the potential to affect quality should be investigated, and the investigation and its conclusions should be documented including all the original details. The validity and extent of all reported quality defects should be assessed in accordance with Quality Risk Management principles in order to support decisions regarding the degree of investigation and action taken. Where appropriate, corrective actions should be taken prior to distribution of blood and blood components or reporting of a test result. The potential impact of the source of the deviation on other components or results should also be considered and preventive action should be taken to eliminate the root cause of the deviation and thereby avoid recurrences.

1.5.5 Investigations should include a review of previous reports or any other relevant information for any indication of specific or recurring problems requiring attention and possibly further regulatory action. Processes and relevant data should be monitored with a view to taking preventive action to avoid potential deviations occurring in the future. Where appropriate, statistical or other tools should be used to assess and monitor process capabilities. As comprehensive information on the nature and extent of the quality defect may not always be available at the early stages of an investigation, the decision-making processes should still ensure that appropriate risk-reducing actions are taken at an appropriate time-point during such investigations.

1.5.6 An appropriate level of root cause analysis work should be applied during the investigation of deviations. In cases where the true root cause(s) cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause of the deviation, this should be formally justified and care should be exercised so as to ensure that process, procedural or system-based errors or problems are not overlooked, if present.

1.5.7 The decisions that are made during and following investigations should reflect the level of risk that is presented by the deviation as well as the seriousness of any non-compliance with respect to the requirements of the blood component specifications or GP. Such decisions should be timely to ensure that patient safety is maintained, in a way that is commensurate with the level of risk that is presented by those issues.

1.5.8 As part of periodic Quality System reviews, an assessment should be made of whether corrective and preventive actions or any re-validation should be undertaken. The reasons for such corrective actions should be documented. Agreed CAPAs should be completed in a timely and effective manner. There should be procedures for the on-going management and review of these actions and the effectiveness of these procedures should be verified during self-inspection.

1.6 Self-inspection, audits and improvements

1.6.1 Self-inspection or audit systems must be in place for all elements of operations to verify compliance with the standards set up by the SFDA. They must be carried out regularly by trained and competent persons, in an independent way, and according to approved procedures.

1.6.2 All results must be documented and appropriate corrective and preventive actions must be taken in a timely and effective manner.​

2.1 Personnel

2.1.1 Personnel must be available in sufficient numbers to carry out the activities related to the collection, testing, processing, storage and distribution of blood and blood components and be trained and assessed to be competent to perform their tasks.

2.1.2 The organization should have an adequate number of personnel with the necessary qualifications and experience. Management has the ultimate responsibility to determine and provide adequate and appropriate resources (human, financial, materials, facilities and equipment) to implement and maintain the Quality Management System and continually improve its suitability and effectiveness through participation in management review. The responsibilities placed on any one individual should not be so extensive as to present any risk to quality. 

2.1.3 There should be an organization chart in which the relationships between key personnel are clearly shown in the managerial hierarchy. Key personnel include the following functions and their substitutes:

        A "Responsible Person"

        A processing manager, responsible for all processing activities;

        A quality control manager, responsible for all quality control activities;

        A quality assurance manager, responsible for ensuring that there are appropriate quality systems and protocols in place for the safe and secure release of all materials, equipment, reagents and blood and blood components;

        A physician with the responsibility for ensuring the safety of donors and a physician or pharmacist with responsibility for the safety of the distributed blood components.

2.1.4 All personnel must have up-to-date signed job descriptions, which clearly set out their tasks and responsibilities. Responsibility for processing management and quality assurance must be assigned to different individuals, and who function independently.

Individual responsibilities should be clearly defined and their correct understanding by individuals should be assessed and recorded. Personnel signature lists should be available.

2.1.5 Personnel in responsible positions should have adequate authority to carry out their responsibilities. Their duties may be delegated to designated deputies of a satisfactory qualification level. There should be no gaps or unexplained overlaps in the responsibilities of those personnel concerned with the application of Good Practice.

2.1.6 All personnel must receive initial and continued training appropriate to their specific tasks. Training record must be maintained. Training programs must be in place and must include Good Practice. Training records should be maintained.

2.1.7 There should be written policies and procedures to describe the approach to training, including a record of training that has taken place, its contents, and its effectiveness.

2.1.8 The contents of training programs must be periodically assessed and the competence of personnel evaluated regularly.

2.1.9 There should be a system of qualifying personnel (competence assessment) involved in key tasks after the appropriate training.

2.2 Hygiene

2.2.1 There must be written safety and hygiene instructions in place, adapted to the activities to be carried out, and are in compliance with standards which are applicable and referenced.

2.2.2 Visitors or untrained personnel should, preferably, not be taken into the processing and laboratory areas. If this is unavoidable, they should be given information in advance, particularly about personal hygiene and the prescribed protective clothing. They should be closely supervised.

2.2.3 It is the organization’s responsibility to provide instructions on hygiene and health conditions that can be of relevance to the quality of blood components (e.g. during collection) and to ensure that staff report relevant health problems. These procedures should be understood and followed in a strict way by all staff members whose duties take them into the processing and laboratory areas. Personnel should be instructed to use the hand-washing facilities.

2.2.4 Steps should be taken to ensure as far as is practicable that no person affected by an infectious disease or having open lesions on the exposed surface of the body is engaged in the preparation of blood components. Medical examinations should be carried out when necessary to assure fitness for work and personal health. There should be instructions ensuring that health conditions that can be of relevance to the quality of blood and blood components are reported by the personnel.

2.2.5 There should be a written policy outlining the requirements for wearing of protective garments in the different areas. The requirements should be appropriate to the activities to be carried out.

2.2.6 Eating, drinking, chewing or smoking, or the storage of food, drink, smoking materials or personal medication in the processing, testing and storage areas should be prohibited. In general, any unhygienic practice within the preparation areas or in any other area where the blood or blood components might be adversely affected should be forbidden.​

​3.1 General

3.1.1 Premises including mobile sites must be located, constructed, adapted and maintained to suit the activities to be carried out. They must enable work to proceed in a logical sequence so as to minimize the risk of errors, and must allow for effective cleaning and maintenance in order to minimize the risk of contamination. The collection of raw material for fractionation or transfusion should be performed in licensed or regulated permanent premises or mobile sites. These sites should be compliant with the intended activity and the current good practice standards approved by the SFDA.

3.1.2 Lighting, temperature, humidity and ventilation should be appropriate and such that they do not adversely affect (directly or indirectly) blood components during their processing and storage, or the accurate functioning of equipment.

3.1.3 Premises should be designed and equipped so as to afford protection against the entry of insects or other animals.

3.1.4 Steps should be taken to prevent the entry of unauthorized people. Areas for processing, laboratory, storage, and quality control should not be used as a right of way by personnel who do not work in them.

    3.1.5. Facilities should permit ease of maintenance and cleaning. Open drains should be avoided.

3.1.6 Preparation areas should be ventilated effectively, with air-control facilities (including   temperature and, if necessary, humidity and filtration) appropriate to the operations undertaken within them and to the external environment. Also, Preparation areas should be suitably lit, particularly where visual checks are carried out.

3.2 Blood donor area

3.2.1 There must be an area for confidential personal interviews with, and assessment of, individuals to assess their eligibility to donate. This area must be separated from all processing areas.

3.2.2 Premises must satisfy common-sense requirements for the health and safety of both the staff (including those of mobile teams) and the donors concerned with due regard to relevant legislation or regulations.

3.3 Blood collection area

3.3.1 Blood collection must be carried out in an area intended for the safe withdrawal of blood from donors that is appropriately equipped for the initial treatment of donors experiencing adverse reactions or injuries from events associated with blood donation. This area must be organized in such a way as to ensure the safety of both donors and personnel as well as to avoid errors in the collection procedure.

3.3.2 Before premises are accepted for mobile donor sessions, their suitability must be qualified against the following criteria:

         Sufficient size to allow proper operation and ensure donor privacy;

         Safety for staff and donors;

         The presence of ventilation, electrical supply, lighting, toilet and hand-washing facilities;

         Reliable communication, blood storage and transport;

         Guarantee of adequate interim storage.

         The arrangement of the collection room and procedures should ensure that blood is collected in a safe and clean environment and to minimize the risk of errors and microbial contamination.

         Consideration should be given to the arrangement of donor beds and the handling of bags, samples and labels.

         There should be trained professionals, medicines, devices and equipment necessary for medical assistance to attend adverse events to the donor and a document that

3.3.3 Donor Canteen/refreshment areas should be available and distinct from the blood collection area. Post donation donors should be supervised in case of adverse events for a reasonable time.

3.4 Blood testing and processing areas

3.4.1 There must be a dedicated laboratory area for testing that is separate from the blood-donor and blood-component processing area, with access restricted to authorized personnel, and must be used only for the intended purpose.

3.4.2 Laboratories should be designed to suit the operations to be carried out in them. Sufficient space should be given to avoid mix-ups and cross-contamination. There should be adequate suitable storage space for samples and records.

3.4.3 Special provisions may be necessary to protect sensitive instruments from vibration, electrical interference, humidity, and extremes of temperature.

3.5 Storage area

3.5.1 Storage areas must provide for appropriately secure and segregated storage of different categories of blood and blood components and materials, including quarantine and released materials as well as units of blood or blood components collected under special criteria (e.g., autologous donation). Access must be restricted to authorized persons.

3.5.2 Provisions must be in place in the event of equipment failure or power failure in the main storage facility.

3.5.3 Storage facilities should be clean and free from litter, dust and pests (e.g., insects, rodents). A pest control program should be in place.

3.5.4 Storage areas should be of sufficient capacity to allow orderly storage of the various categories of materials and blood components including packaging materials, intermediate and finished components, and materials in quarantine, released, rejected, returned or recalled.

3.5.5 Storage areas should be designed or adapted to ensure good storage conditions. In particular, they should be clean and dry and maintained within predefined temperature limits. Where special storage conditions are required (e.g. temperature, humidity) these should be provided, checked and monitored. An alarm system should alert users in a timely manner to any excursion outside predefined limits.

3.5.6 Receiving and dispatch bays should protect materials and products from the weather. Reception areas should be designed and equipped to allow containers of incoming materials to be cleaned where necessary before storage. The reception area should be separate from the storage area.

3.5.7 If quarantine status is ensured by storage in separate areas, these areas must be marked clearly and their access restricted to authorized personnel. Any system replacing the physical quarantine (e.g., computerized system) should provide equivalent security. Furthermore, Segregated areas should be allocated and identified appropriately for storage of rejected, discarded, recalled or returned materials, or blood and blood components.

3.6 Ancillary areas

3.6.1 Staff rest and refreshment areas should be separate from other rooms. Also, facilities for changing clothes and for washing and toilet purposes should be readily accessible and appropriate for the number of users. Toilets should not directly open to processing, laboratory or storage areas.

3.6.2 Maintenance workshops should, as far as possible, be separated from preparation areas. If parts and tools are stored in processing and laboratory areas, they should be kept in a location reserved for that use.

3.7 Waste disposal area

3.7.1 An area must be designated for the safe disposal of waste, disposable items used during collection, testing and processing and for rejected blood or blood components.

3.7.2 The transfer of medical waste within and outside the facility, and according to the common system of Health Care waste management for the Gulf Cooperation Council of the Arabian Gulf countries, corresponding to the implementation by the royal decree No. (M/53) dated 16/9/1426H.​

​4.1 General requirements

4.1.1 All equipment must be calibrated and qualified, and maintained to suit its intended purpose. Operating instructions must be available and appropriate records kept.

4.1.2 Equipment must be selected to minimize any hazard to donors, personnel or blood components.

4.1.3 All validated processes must use qualified equipment. Qualification results must be documented. Regular maintenance and calibration must be carried out and documented according to established procedures. The maintenance status of each item of equipment must be available.

4.1.4 All critical equipment must have regular, planned maintenance to detect or prevent avoidable errors and keep the equipment in its optimum functional state. The maintenance intervals and actions must be determined for each item of equipment.

4.1.5 New and repaired equipment must meet qualification requirements when installed and must be authorized before use.

4.1.6 All modifications, enhancements or additions to validated systems and equipment must be managed through the change control procedure of the blood establishment. The effect of each change to the system or equipment, as well as its impact on quality and safety, must be determined to identify the extent of re-validation required. 

4.1.7 Instructions for use, maintenance, servicing, cleaning and sanitation must be available.

4.1.8 Procedures must be available for each type of equipment that detail the action to be taken if malfunctions or failures occur.

4.1.9 Only reagents and materials from approved suppliers that meet the documented requirements and specifications must be used. Critical materials must be released by a person qualified to perform this task.

4.1.10 Manufacturers of sterile materials (e.g. blood bag systems, anticoagulant solutions) should provide a certificate of release for each batch. The blood establishment should define acceptance criteria for such certificates in writing, and should include at least the name of the material, manufacturer, compliance with relevant requirements (e.g. pharmacopoeias or regulations for medical devices) and confirmation that the materials are sterile and pyrogen- free.

4.1.11 Status of materials (quarantined, released, rejected) should be clearly indicated.

4.1.12 Materials and reagents should be stored under stated manufacturer conditions and in an orderly manner that permits segregation by batch and lot as well as stock rotation.

4.1.13 Storage and use of materials should follow the ‘first-in first-out’ principle (i.e. the material that entered storage first should be used first) taking into account the expiry date of materials.

4.1.14 Inventory records must be retained for a period acceptable to and agreed with the SFDA.

4.1.15 Equipment and material inventory records must be kept as a means to build up a history for a processed component to facilitate recalls.

4.1.16 Repair and maintenance operations should not present any hazard to the donor, staff or quality of the blood and blood components.

4.1.17 Equipment should be designed or selected so that it can be thoroughly cleaned (and where necessary decontaminated). This should be performed according to detailed and written procedures. It should be stored only in a clean and dry condition.

4.1.18 Washing/cleaning solutions and equipment should be chosen and used so that they are not sources of contamination.

4.1.19 Equipment should be installed in such a way as to prevent any risk of error or of contamination.

4.1.20 Parts of equipment and materials that come into contact with blood and blood components must not be reactive, additive or absorptive to such an extent that they affect the quality of the component and thus present any hazard.

4.1.21 Balances and measuring equipment of an appropriate range and precision should be available. Equipment for measuring, weighing, recording and control should be calibrated and checked at defined intervals using appropriate methods. Adequate records of such tests should be maintained, including the values obtained prior to any adjustment. Calibration reports should include the accuracy of any testing equipment and traceability to a national standard. The report and/or calibration certificate must be reviewed and signed to show acceptance of the document. Any failed calibrations will require mention of non-conformance to investigate the potential impact.

4.1.22 Defective equipment should be labelled clearly as such and, if possible, removed from preparation areas.

4.2. Data processing systems  

4.2.1. If computerized systems are used, software, hardware and back-up procedures should be checked regularly to ensure reliability, be validated before use, and be maintained in a validated state. Hardware and software should be protected against unauthorized use or unauthorized changes. The back-up procedure should prevent loss of or damage to data at expected and unexpected downtimes or function failures. 

4.2.2. Systems should be properly maintained at all times. Documented maintenance plans should be developed and implemented. This strategy should include audits of quality assurance systems.

4.2.3. Changes in computerized systems should be validated; applicable documentation should be revised and relevant personnel trained appropriately, before any change is introduced into routine use. Computerized systems should be maintained in a validated state. This should include user-testing to demonstrate that the system is correctly performing all specified functions both at initial installation and after any system modifications. 

4.2.4. There should be a hierarchy of permitted user access to enter, amend, read or print data. Methods of preventing unauthorized entry should be in place, such as personal identity codes or passwords that are changed regularly. 

4.2.5. All necessary measures should be taken to ensure protection of data. These measures should ensure that safeguards against unauthorized additions, deletions or modifications of data and transfer of information are in place to resolve data discrepancies, and to prevent unauthorized disclosure of such information. 

4.2.6. Computer systems designed to control decisions related to inventories and release of blood components should prevent the release of all blood or blood components considered not acceptable for release. Preventing release of any components from a future donation from a deferred donor should be possible. ​

4.3 Qualification and validation

4.3.1 General principles

4.3.1.1 Facilities and equipment need to be qualified prior to implementation. Systems, processes and tests should be validated, which involves wider consideration beyond the facilities and equipment used. In this document, however, the term validation is used in a generic sense, encompassing both qualification and validation activities.

4.3.1.2 The principles of qualification and validation are applicable to the collection, preparation, testing, packaging, distribution and issuance of blood components. Blood establishments and hospital blood banks must control the critical aspects of their operations through the life cycle of the blood components and the associated processes. Any planned changes to the facilities, equipment, utilities and processes should be formally documented and the impact on the quality on blood components should be validated.

4.3.1.3 A quality risk management approach, consisting of a systematic process for the assessment, control, communication and review of risks to quality across the lifecycle of the blood component, should be applied. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes.

4.3.1.4 Data supporting qualification and/or validation studies which were obtained from sources outside of the blood establishment/hospital blood banks own quality system may be used provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.

4.3.2. Organizing and planning for validation 

4.3.2.1 All qualification and validation activities should be planned and take the life cycle of facilities, equipment, utilities, process and product into consideration.

4.3.2.2 Qualification and validation activities should only be performed by suitably trained personnel who follow approved procedures and report as defined in the blood establishment quality system. There should be appropriate quality oversight over the whole validation life cycle.

4.3.2.3 The key elements of the site qualification and validation programme should be clearly defined and documented in a validation master plan (VMP) or equivalent document.

4.3.2.4 The VMP or equivalent document should define the qualification/validation system and include or reference information on at least the following:

        o Qualification and validation policy;

        o The organizational structure including roles and responsibilities for qualification and validation activities;

        o Summary of the facilities, equipment, systems, processes on site and their qualification and validation status;

        o Change control and deviation management for qualification and validation;

        o Guidance on developing acceptance criteria;

        o References to existing documents;

        o The qualification and validation strategy, including requalification, where applicable.

4.3.2.5. For large and complex projects, planning takes on added importance and separate validation plans may enhance clarity. These should be linked and traceable. 

4.3.2.6. A quality risk management approach should be used for qualification and validation activities. In light of increased knowledge and understanding from any changes during the qualification and validation phase, the risk assessments should be repeated, as required. The way in which risk assessments are used to support qualification and validation activities should be clearly documented. 

4.3.2.7 Appropriate checks should be incorporated into qualification and validation work to ensure the integrity of all data obtained. 

4.3.3. Documentation including VMP 

4.3.3.1 Good documentation practices are important to support knowledge management throughout the product lifecycle. Validation protocols should be prepared which specify how qualification and validation should be performed and which define the critical systems, attributes and parameters and the associated acceptance criteria. 

4.3.3.2. All documents generated during qualification and validation should be approved and authorized by appropriate personnel as defined in the quality system. 

4.3.3.3. Qualification documents may be combined together, where appropriate, e.g., installation qualification (IQ) and operational qualification (OQ). 

4.3.3.4. Any significant changes to the approved protocol during execution, e.g., acceptance criteria, operating parameters etc., should be documented as a deviation and be scientifically justified. 

4.3.3.5. The interrelationship between documents in complex validation projects should be clearly defined.

4.3.3.6. Where validation protocols and other documentation are supplied by a third-party providing validation services, appropriate personnel at the blood establishment should confirm suitability and compliance with internal procedures before approval. Vendor protocols may be supplemented by additional documentation/test protocols before use. 

4.3.3.7. Results which fail to meet the pre-defined acceptance criteria should be recorded as a deviation and be fully investigated according to local procedures. Any implications for the validation should be discussed in the report. 

4.3.3.8. The review and conclusions of the validation should be reported and the results obtained summarized against the acceptance criteria. Any subsequent changes to acceptance criteria should be scientifically justified and a final recommendation made as to the outcome of the validation. 

4.3.3.9. A formal release for the next stage in the qualification and validation process should be authorized by the relevant responsible personnel either as part of the validation report approval or as a separate summary document. Conditional approval to proceed to the next qualification stage can be given where certain acceptance criteria or deviations have not been fully addressed and there is a documented assessment that there is no significant impact on the next activity. 

4.3.4. Qualification stages for equipment, facilities, and systems 

Qualification activities should consider all stages from initial development of the user requirements specification through to the end of use of the equipment, facility or system. The main stages and some suggested criteria (although these depend on individual project circumstances and may be different) which could be included in each stage are indicated below. 

4.3.4.1 Installation Qualification (IQ): It should be performed on new or modified facilities, systems and equipment. IQ should include, but is not limited to, the following:

         Installations of components, equipment, piping, services and instrumentation, which are checked against up-to-date engineering drawings and specifications; 

         Verification of the correct installation against pre-defined criteria;

         Collection and collation of supplier operating and working instructions and maintenance requirements; 

         Calibration requirements; 

         Verification of construction materials.

4.3.4.2 Operational Qualification (OQ): The completion of a successful OQ should allow finalization of calibration, operating and cleaning procedures, operator training and preventive maintenance requirements. OQ normally follows IQ but depending on the complexity of the equipment, it may be performed as a combined Installation/Operation Qualification (IOQ). OQ should include, but is not limited to, the following: 

         Tests that have been developed from knowledge of processes, systems and equipment to ensure the system is operating as designed; 

         Tests to confirm upper and lower operating limits, and /or “worst case” conditions. 

4.3.4.3 Performance Qualification (PQ): Although PQ is described as a separate activity, in some cases it may be appropriate to perform it in conjunction with OQ or Process Validation. PQ should follow successful completion of IQ and OQ. 

PQ should include, but is not limited to, the following: 

         Tests, using production materials, qualified substitutes or simulated blood components proven to have equivalent behavior, under normal and worst-case operating conditions. The frequency of sampling used to confirm process control should be justified; 

         Tests should cover the operating range of the intended process, unless documented evidence from the development phases confirming the operational ranges is available.

4.3.5 Re-qualification

4.3.5.1 Equipment, facilities and systems should be evaluated at an appropriate frequency to confirm that they remain in a state of control.

4.3.5.2 Where re-qualification is necessary and performed over a specific time period, the period should be justified and the criteria for evaluation defined. Furthermore, the possibility of small changes over time should be assessed.

4.4 Control of equipment and materials 

4.4.1 General principles 

4.4.1.1. Documented systems for purchasing equipment and materials should be available. These should identify the specific requirements for establishing and reviewing contracts for the supply of both equipment and materials. 

4.4.1.2 The contracting process should include: 

         Checks prior to awarding the contract to help ensure suppliers meet the organization’s needs; 

         Appropriate checks on received goods to confirm they meet specifications; 

         The requirement for manufacturers to provide a certificate of analysis for critical material; 

         Checks to ensure that goods in use continue to meet specifications; 

         Regular contact with suppliers to help understand and resolve problems; 

         Performance of regular audits. 

         Assessment of the performance of equipment should occur in the following situations: 

         Upon commissioning of new equipment, which should include design, installation, operational and performance qualifications, and full validation data from the manufacturer; 

         After any relocation, repairs or adjustments that might potentially alter equipment functioning; 

         If ever a doubt arises that, the equipment is not functioning appropriately. 

         Consideration should be given to the quality, safety and efficacy of any blood components prepared before discovery of the fault adjustment. 

4.4.2 Calibration and monitoring of equipment 

4.4.2.1 It is necessary to establish a mechanism to ensure the adequacy of the calibration and monitoring programs, and that qualified personnel are available for their implementation. A calibration and monitoring plan should be used to define the requirements for establishing and implementing a calibration program that includes the frequency of monitoring. 

4.4.2.2 Trending and analyses of calibration and monitoring results should be a continuous process. Intervals of calibration and monitoring should be determined for each item of equipment to achieve and maintain a desired level of accuracy and quality. The calibration procedure should be based on a recognized international standard. The calibration status of all equipment that requires calibration should be readily available. 

4.4.2.3 To ensure appropriate performance of a system or equipment, a monitoring plan should be developed and implemented. The plan should take into account the criticality of the system or equipment, and should outline monitoring, user-notification and problem-resolution mechanisms. If an unusual event is observed, personnel should follow the standard response described in the monitoring plan. The standard response should involve notifying affected personnel and, possibly, initiation of a resolution response to the problem and risk assessment of the affected blood components. Depending on the severity of the problem and the criticality of the system or equipment, a back-up plan may need to be implemented to keep the process or system operating. 

4.4.2.4 In addition to testing that evaluates the suitability of the implemented changes, sufficient validation should be conducted on the entire system to demonstrate that portions of the system not involved in the change are not adversely impacted. 

4.4.2.5 The training program should be reassessed for any critical change in environment, equipment or processes. Training records (including plans and protocols of training status) should ensure that training needs are identified, planned, delivered and documented appropriately for maintenance of validated systems and equipment. 

4.4.2.6 A periodic review process should be established to ensure that documentation for the system or equipment is complete, current and accurate. A report of the review process should be produced. When deviations or problems are found, actions should be identified, prioritized, planned and implemented.​

5.1 General principles

5.1.1 The requirements and principles outlined in this section are applicable to the preparation, distribution and issuance of blood components. They cover the initial validation of new processes, subsequent validation of modified processes or site transfers for maintaining of the validated state (ongoing process verification). It is implicit in this section that a robust product development process is in place to enable successful process validation.

5.1.2 Processes should be shown to be robust and ensure consistent blood component quality prior to their distribution and routine clinical use. Processes should undergo a prospective validation program, wherever possible. Retrospective validation is no longer an acceptable approach.

5.1.3 Process validation of new blood components should cover all intended processes and sites of manufacture. A scientific and risk-based validation approach could be justified for new blood components based on extensive process knowledge from the development stage in conjunction with an appropriate ongoing statistical process control. The design assumes that the validation performed is representative for all process or product settings.

5.1.4 For validation of processes for preparation of blood components that are transferred from one site to another or within the same site, the number of blood components used for process validation could be reduced based on existing process knowledge, including the content of the previous validation that should be available. The same approach may be used for different blood bag sizes or volumes, if justified.

5.1.5 Process validation should establish whether all quality attributes and process parameters, which are considered important for ensuring the validated state and acceptable blood component quality, can be consistently met by the process. A critical quality attributes (CQA) is a physical, chemical, biological or microbiological property or characteristic that should be within an approved limit, range or distribution to ensure the desired component quality. A critical process parameter (CPP) is a process parameter whose variability has an impact on a critical quality attribute and which therefore should be monitored or controlled to ensure the process produces the desired quality. The basis by which process parameters and quality attributes were identified as being critical or non-critical should be clearly documented, taking into account the results of any risk assessment activities.

5.1.6 The facilities, systems and equipment to be used should be qualified before use and analytical testing methods should be validated. Facilities, systems, equipment, utilities and processes should be periodically evaluated to ensure that they are still operating appropriately.

5.1.7 For all blood components, process knowledge from development studies or other sources should be accessible to the blood establishment, unless otherwise justified, and be the basis for validation activities.

5.1.8 During process validation a variety of personnel may be involved in the preparation of blood components. Blood components should only be prepared by trained personnel in accordance with good practice using approved documentation. It is expected that processing personnel are involved in the preparation of blood components during validation to facilitate understanding of the process.

5.1.9 The suppliers of critical materials should be qualified prior to the preparation of blood components during process validation; otherwise, a justification based on the application of quality risk management principles should be documented.

5.1.10 Where blood components prepared during process validation are released for clinical use, this should be pre-defined. The conditions under which they are produced should fully comply with the requirements of Good Practice, with the validation acceptance criteria and with any continuous process verification criteria (if used).​

5.2 Concurrent validation

5.2.1 In exceptional circumstances and justified on the basis of significant patient benefit, where there is a strong benefit-risk ratio for the patient and with systematic control of each blood component unit for their conformity to regulatory requirements, it may be acceptable to execute the validation protocol concurrently with distribution of the units produced during validations and not to complete a validation program before routine production. However, the decision to carry out concurrent validation should be documented in the VMP for visibility and approved by authorized personnel.

5.2.2 Where a concurrent validation approach has been adopted, there should be sufficient data to support a conclusion that any given blood component meets the defined acceptance criteria. The results and conclusion should be formally documented and available to the Responsible Person prior to release for clinical use.

5.3 Prospective validation

5.3.1 Using this approach, a number of blood components may be prepared under the proposed new conditions. The number of processes runs carried out, the number of samples taken and the number of observations made should be based on quality risk management principles and be sufficient to allow the normal range of variation and trends to be established and to provide sufficient data for evaluation. Each blood establishment should determine and justify the number of blood component units necessary to demonstrate assurance that the process is capable of consistently delivering quality blood components.

5.3.2 Preparation of blood components during the validation phase should reflect the numbers intended to be produced under normal production circumstances.

A process validation protocol should be prepared which defines the critical process parameters (CPP), critical quality attributes (CQA) and the associated acceptance criteria which should be based on development data or documented process knowledge.

5.3.3 Process validation protocols should include, but are not limited to the following:

        o Short description of the process;

        o Functions and responsibilities;

        o Summary of the CQAs to be investigated;

        o Summary of CPPs and their associated limits;

        o Summary of other (non-critical) attributes and parameters which will be investigated or monitored during the validation activity, and the reasons for their inclusion;

        o List of the equipment/facilities/personnel to be used (including measuring/monitoring/recording equipment) together with the calibration status;

        o List of analytical methods and method validation, as appropriate;

        o Proposed in-process controls with acceptance criteria and the reason(s) why each in- process control is selected;

        o Additional testing to be carried out with acceptance criteria;

        o Sampling plan and the rationale behind it;

        o Methods for recording and evaluating results;

        o Process for release and certification of units (if applicable);

        o Conclusion.

5.4. Ongoing process, verification and maintenance of the validated state 

5.4.1 Ongoing process verification should provide documented evidence, using statistical process control that the process remains in a state of control during routine manufacture.

5.4.2 All critical processes should be constantly monitored and periodically evaluated to confirm that they remain valid. Where no significant changes have been made to the validated status, a review with evidence that the process meets the prescribed requirements may be deemed acceptable in place of a full re-validation.

5.4.3 Blood establishments should monitor blood component quality using statistical process control to ensure that a state of control is maintained throughout the blood component lifecycle with the relevant process trends evaluated.

5.4.4 The extent and frequency of ongoing process verification should be reviewed periodically. At any point throughout the product life-cycle, it may be appropriate to modify the requirements taking into account the current level of process understanding and process performance.

5.4.5 Ongoing process verification should be conducted under an approved protocol or equivalent documents and a corresponding report should be prepared to document the results obtained. Statistical tools should be used, where appropriate, to support any conclusions with regard to the variability and capability of a given process and ensure a state of control.

5.4.6 The following items are essential to maintain a validated state:

        o Calibration and monitoring;

        o Preventive maintenance;

        o Training and competency;

        o Supplier re-qualification;

        o Periodic review;

        o Performance monitoring;

        o System retirement.

5.4.7 Maintenance of the validated status of the blood components should be documented in the Product Quality Review. Incremental changes over time should also be considered and the need for any additional actions, e.g., enhanced sampling, should be assessed.

5.4.8 Operational change control, document control and quality control procedures support the maintenance of the validated state.

​6.1 General principles

Quality monitoring of blood components should be consistent with the current specifications for in-process and finished components.

6.1.1 The processing of blood components must be carried out using appropriate and validated procedures, including measures to avoid the risk of contamination and microbial growth in the prepared blood components.

6.1.2 The use of closed systems is strongly recommended for all steps in component processing. Open systems may exceptionally be necessary due to local constraints and should be undertaken in an environment specifically designed to minimize the risk of bacterial contamination. When open systems are used, careful attention should be given to the use of aseptic procedures.

6.1.3 Validation of freezing processes should consider worst-case scenarios that take into account minimum and maximum loads and positions in the freezer.

6.1.4 Sterile connecting devices must be used in accordance with a validated procedure. When validated, connections made using sterile connecting devices are regarded as closed system processing. The resulting weld must be checked for satisfactory alignment and its integrity must be confirmed.

6.2 Preparation/Process record

6.2.1 Each unit is considered to be a unique batch, but preparation records should provide sufficient information to build the history and traceability of a prepared component. Usually this information is captured in the computerized systems of the blood establishment. In general, the blood establishment should have access to the following processing records for each unit:

        o The name and unique identifier of the component;

        o The dates and times of commencement of significant intermediate stages and of completion of processing:

        o The identification (initials) of the operator(s) who performed each critical step of the process (including the process controls) and, where appropriate, the name of any person who verified such steps;

        o The batch number of any relevant consumables and/or analytical control number of each consumable;

        o A record of the in-process controls and identity of the person(s) carrying them out, as well as the results obtained;

        o The results of testing undertaken on the donation and/or the component (excluding quality monitoring);

        o Notes on any deviation, including details of the procedures with signed authorization;

        o Information on the processing of non-standard components with signed authorization.​

6.3 Validation of test methods

6.3.1 All analytical test methods used in qualification or validation exercises should be validated with an appropriate detection and quantification limit, where necessary.

6.3.2 Where microbial testing of blood components is carried out, the method should be validated to confirm that the product or residues, e.g. antibiotics, do not interfere with the analysis and influence the recovery of microorganisms.

6.3.3 Where microbial testing of surfaces is carried out, validation should be performed on the test method to confirm that sanitizing agents do not influence the recovery of microorganisms.

6.4 Preparation instructions

Approved, written instructions for preparation should exist for each type of component that is produced. These should include:

        o A process flow for each stage in the preparation of the component, including where it is undertaken and any critical equipment used;

        o Methods (or reference to the methods) to be used for starting up and maintaining critical equipment (e.g. cleaning, assembly, calibration);

        o The requirement to check that the equipment and work station are clear of previous blood components, documents or materials not required for the planned process, and that equipment is clean and suitable for use;

        o Detailed stepwise processing instructions (e.g. checks on materials, pre-treatments, sequence for adding materials, and critical process parameters such as time and temperature);

        o The instructions for any in-process controls with their limits;

        o Requirements for storage of the components and any critical materials and consumables;

        o Any special precautions to be observed.

6.5 Change control

6.5.1 Change control procedures should ensure that sufficient supporting data are generated to demonstrate that the revised process results in a blood component of the desired quality, consistent with the approved specifications. Supporting data, e.g. copies of documents, should be reviewed to confirm that the impact of the change has been demonstrated prior to final approval.

6.5.2 Written procedures should be in place to describe the actions to be taken if a planned change is proposed for a starting material, blood component specification, process, equipment, environment (or site), product range, method of production or testing or any other change that may affect donor safety, blood component quality or reproducibility of the process.

6.5.3 Changes should be authorized and approved by the responsible persons or relevant functional personnel in accordance with the blood establishment’s quality system.

6.5.4 Quality risk management should be used to evaluate planned changes to determine the potential impact on blood component quality, the blood establishment’s quality systems,

documentation, validation, regulatory status, calibration, maintenance and on any other system to avoid unintended consequences and to plan for any necessary process validation, verification or requalification efforts.

6.5.5 Following implementation, where appropriate, an evaluation of the effectiveness of change should be carried out to confirm that the change has been successful.

6.5.6 Some changes may require notification to, or license amendment, from a national regulatory authority. 

There should be appropriately authorized and dated specifications for starting and packaging materials, as well as finished blood and blood components.

Specifications for starting and primary or printed packaging materials should include or provide reference to, if applicable:

       o A description of the materials, including:

       o The designated name and the internal code reference;

       o The approved suppliers and, if reasonable, the original producer of the material;

       o A sample of printed materials;

       o Directions for sampling and testing;

       o Qualitative and quantitative requirements with acceptance limits;

       o Storage conditions and precautions;

       o The maximum period of storage before re-examination. 

Specifications for in-process and finished components should be available

Component monographs contained in the Guide to the preparation, use and quality assurance of blood components published by the Council of Europe may be used). Components must be labelled in accordance with European Directive 2002/98/EC.​

​8.1 At all stages of the preparation, lab​elling should identify the individual components and their nature clearly.

8.2 Requirements for in-process labelling. The label on an intermediate component should always allow the stage of processing to be determined and should always include:

           o The name of the component;

           o The unique numeric or alpha-numeric donation identification;

           o The name of the producing blood establishment.

8.3 At all stages, all containers must be labelled with relevant information on their identity. In the absence of a validated computerized system for status control, the labelling must clearly distinguish released from non-released units of blood and blood components.

8.4 Type of label to be used (shall be appropriate to the storage conditions and ensuring safety of the product), as well as the labelling methodology, should be defined and established in written Standard Operating Procedures.

8.5 Labels applied to containers, equipment or premises should be clear, unambiguous and in the agreed format of the blood establishment.

8.6 Labelling system for collected blood, intermediate and finished blood components, and samples must unmistakably identify the type of content, and comply with the labelling and traceability requirements.

8.7 Blood establishments responsible for the preparation of blood components must provide clinical users of blood components with information on their use, composition, and any special conditions that do not appear on the component label.

8.8 For autologous blood and blood components, the label must also comply with additional requirements for autologous donations.

8.9 The label for a finished blood component should comply with the requirements of the National Regulator requirements and includes at least the following information:

           o The unique donation number.

           o The product name.

           o The required storage conditions

           o The expiry date.

           o The date of collection of the donation

           o The date and time of irradiation (where applicable)

           o The ABO and RhD blood group

           o The name or other identification of the component preparation site.

9.1 There must be a safe and secure system to prevent any single blood sample and blood component from being released before all mandatory requirements set out have been fulfilled. 

9.2 Each blood establishment must be able to demonstrate that each blood or blood component has been formally released by an authorized person. Records must demonstrate that before a blood component has been released, all current declaration forms, relevant medical records, and test results have met all acceptance criteria.

9.3 If a computerized system is used to release results from the laboratory, an audit trail should indicate who was responsible for their release. 

9.4 There should be Standard Operating Procedures that detail the actions and criteria that determine whether the blood or blood component can be released. The release criteria and specifications of blood components should be defined, validated, documented and approved.

9.5 There should be a defined procedure for exceptional release of non-standard blood and blood components under a planned non-conformance system. The decision to allow such release should be documented clearly and traceability should be ensured.

9.6 Before release, blood and blood components must be kept administratively and physically segregated from released blood and blood components. In the absence of a validated computerized system for status control, the label of a unit of blood or blood component must identify the release status.

9.7 There should be a system of administrative and physical quarantine for blood and blood components to ensure that components cannot be released until all mandatory requirements have been met.

9.8 Where release is subject to computer-derived information the following points should be checked: 

          The computer system should be validated to be fully secure against the possibility of blood and blood components which do not fulfil all test or donor selecting criteria, being released; 

          The manual entry of critical data, such as laboratory test results, should require independent verification and release by a second authorized person; 

          There should be a hierarchy of permitted access to enter, amend, read or print data. Methods of preventing unauthorized entry should be available, such as personal identity codes or passwords which are changed on a regular basis.

         ​ The computer system should block the release of all blood or blood components considered not acceptable for release. There should also be a means to prevent a donor from being accepted as a future donor. 

9.9 Before they are destroyed, blood and blood components not acceptable for release should be quarantined in a secured storage facility. 

9.10 Before final product release, if blood or blood component(s) have been prepared from a donor who has donated on previous occasions, a comparison with previous records should be made to give assurance that current records accurately reflect the donor history.

9.11 In the event that the final component fails to be released due to a confirmed positive test result for infection for an agent mentioned in Annex I, a check must be made to ensure that other components from the same donation and components prepared from previous donations given by the donor have been identified. An immediate update must be made to the donor record. In the event that a final component fails release due to a potential impact on patient safety, the donor record must be immediately updated to ensure, where appropriate, that the donor(s) cannot make a further donation.

10.1 The Quality System of the blood establishment should ensure that, for blood and blood components intended for the manufacture of medicinal products, the requirements for storage and distribution should comply with legal requirements.

10.2 Procedures for storage and distribution must be validated to ensure the quality of blood and blood components during the entire storage period, and to exclude mix-ups of blood components. All transportation and storage actions, including receipt and distribution, must be defined by written procedures and specifications.

10.3 Storage conditions must be controlled, monitored and checked. Appropriate alarms must be present and checked regularly; all checks must be recorded. Appropriate actions on alarms must be defined.

10.4 There should be a system to ensure stock rotation involving regular and frequent checks that the system is operating correctly. Blood and blood components beyond their expiry date or shelf-life should be separated from usable stock. Before distribution, blood components must be visually inspected. 

10.5 Autologous blood and blood components, as well as blood components collected and prepared for specific purposes, must be stored separately. Appropriate records of inventory and distribution must be kept.

10.6 Records should be kept of the distribution of blood components between blood establishments, blood establishments and hospital blood banks and between hospital blood banks. These records should show the date of supply, unique component identifier and name of the blood component, the quantity received or supplied, name and address of the supplier or consignee.

10.7 Packaging must maintain the integrity and storage temperature of blood and blood components during distribution and transportation.​

11.1 Blood components should be transported in accordance with the defined and documented conditions depending on the type of product.

11.2 It is recognised that verification of transportation may be challenging due to the variable factors involved however, transportation routes should be clearly defined. Seasonal and other variations should also be considered during verification of transport.

11.3 A risk assessment should be performed to consider the impact of variables in the transportation process other than those conditions which are continuously controlled or monitored, e.g., delays during transportation, failure of cooling and/or monitoring devices, blood component susceptibility and any other relevant factors.

11.4 Due to the variable conditions expected during transportation, continuous monitoring and recording of any critical environmental conditions to which the blood component may be subjected should be performed, unless otherwise justified.

11.5 Return of blood and blood components into inventories for subsequent re-issue must be allowed only if all requirements and procedures relating to quality as laid down by the blood establishment to ensure the integrity of blood components are fulfilled.

11.6 Blood components must not be returned to the blood establishment for subsequent distribution unless there is a procedure for the return of blood components that is regulated by a contract, and if there is, documented evidence for each returned blood component that the agreed storage conditions have been met. Before subsequent distribution, records must identify that the blood component has been inspected before re-issue.​

12.1 General principles

12.1.1 Tasks that are performed externally by a third party must be defined in a specific written contract. Outsourced activities that may impact on the quality, safety or efficacy of the blood components should be correctly defined, agreed and controlled in order to avoid misunderstandings which could result in a blood component or work of unsatisfactory quality. There should be a written contract covering these activities, the products or operations to which they are related, and any technical arrangements made in connection with it.

12.1.2 All outsourced arrangements for blood collection, processing and testing, including any proposed changes, should be done in accordance with a written contract, with reference to the specification for the blood or blood component(s) concerned.

12.1.3 There should be a contract/agreement between the blood bank and the laboratory conducting the mandatory tests. The contracted laboratory shall not sub-contract all or any part of the contract to a third party without the consent of the bank, to which it is contracted. The sub- contracted laboratory shall have a SFDA license for the tests involved.

12.1.4 The responsibilities of each party should be documented to ensure that current Good Practice principles are maintained.

12.2 The contract giver

12.2.1 The contract giver is responsible for assessing the competence of the contract acceptor to successfully carry out the work being outsourced and for ensuring, by means of the contract, that the principles and guidelines of Good Practice are followed.

12.2.2 The contract giver should provide the contract acceptor with all the information necessary to carry out the contracted operations correctly and in accordance with the specification and any other legal requirements. The contract giver should ensure that the contract acceptor is fully aware of any problems associated with the materials, samples or the contracted operations that might pose a hazard to the premises, equipment, personnel, other materials or other blood components of the contract acceptor.

12.2.3 The contract giver should ensure that all blood and blood components, analytical results and materials delivered by the contract acceptor comply with their specifications and that they have been released under a Quality System approved by the Responsible Person or other authorized person.

12.3 The contract acceptor

12.3.1 The contract acceptor should have adequate premises, equipment, knowledge, experience and competent personnel to satisfactorily carry out the work requested by the contract giver and shall comply with requested standards.

12.3.2 The contract acceptor should ensure that all products, materials or test results delivered by the contract giver are suitable for their intended purpose.

12.3.3 The contract acceptor should not pass to a third party any of the work entrusted under the contract without the contract giver’s prior evaluation and approval of the arrangements. Arrangements made between the contract acceptor and any third party should ensure that the relevant blood collection, processing and testing information is made available in the same way as between the original contract giver and contract acceptor.

12.3.4 The contract acceptor should refrain from any activity that may adversely affect the quality of the blood and blood components prepared and/or analyzed for the contract giver.

12.4 The contract

12.4.1 A contract should be drawn up between the contract giver and the contract acceptor that specifies their respective responsibilities relating to the contracted operations. All arrangements for blood collection, processing and testing should be in compliance with the requirements of Good Practice and regulatory requirements and agreed by both parties.

12.4.2 The contract should specify the procedure, including the necessary requirements to be provided by the contract acceptor, by which the Responsible Person or other authorized person releasing the blood and blood components for sale or supply can ensure that each component has been prepared and/or distributed in compliance with the requirements of Good Practice and regulatory requirements.

12.4.3 The contract should clearly describe who is responsible for purchasing materials, testing and releasing materials, undertaking blood collection, and for processing and testing (including in- process controls). In the case of sub-contracted analyses, the contract should state the arrangements for the collection of samples and the contract acceptor should understand that they may be subject to inspections by the SFDA.

12.4.4 Preparation and distribution records, including reference samples if relevant, should be kept by, or be available to, the contract giver. Any records relevant to assessment of the quality of the blood or a blood component in the event of complaints or a suspected defect should be accessible and specified in the defect/recall procedures of the contract giver.

12.4.5 The contract should permit the contract giver to audit the facilities of the contract acceptor.​

​13.1 General principles

13.1.1 Blood components deviating from prevalent Good Practices shall be released for transfusion only in exceptional circumstances and with the recorded agreement of the prescribing physician and the blood establishment physician.

13.1.2 There should be a defined procedure for the release of non-standard blood and blood components under a planned non-conformance system. The decision for such release should be clearly documented and authorised by a designated person and traceability should be ensured.

13.1.3 There should be systems in place to ensure that deviations, adverse events, adverse reactions and non-conformances are documented, carefully investigated for causative factors of any defect and, where necessary, followed up by the implementation of corrective actions to prevent recurrence.

13.1.4 The corrective and preventive actions (CAPAs) system should ensure that existing component non-conformity or quality problems are corrected and that recurrence of the problem is prevented.

13.1.5 Deviations from established procedures should be avoided as much as possible and should be documented and explained. Any errors, accidents or significant deviations that may affect the quality or safety of blood and blood components should be fully recorded and investigated in order to identify systematic problems that require corrective action. Appropriate corrective and preventive actions should be defined and implemented.

13.1.6 Investigations relating to serious deficiencies, significant deviations and serious component quality defects should include an assessment of component impact, including a review and evaluation of relevant operational documentation and an assessment of deviations from specified procedures.

13.1.7 There should be procedures for notifying responsible management in a timely manner of deficiencies, deviations or non-compliances with regulatory commitments (e.g. in submissions and responses to regulatory inspections), component or product quality defects, or testing errors and related actions (e.g. quality related complaints, recalls, regulatory actions, etc.).

13.1.8 Executive management and the Responsible Person should be notified in a timely manner of serious deficiencies, significant deviations and serious component or product quality defects and adequate resource should be made available for their timely resolution.

13.1.9 A regular review of all significant deviations or non-conformances should be conducted, including their related investigations, to verify the effectiveness of the corrective and preventive actions taken.

13.2 Complaints and Serious Adverse Event and Reaction

13.2.1 All complaints and other information, including serious adverse reactions and serious adverse events that may suggest that defective blood components have been issued, must be documented, carefully investigated for causative factors of the defect and, where necessary, followed up by recall and the implementation of corrective actions to prevent recurrence. An appropriate Operating Procedure shall be in place. Procedures must be in place to ensure that National regulator is notified immediately of serious adverse reactions or serious adverse events.

13.2.2 A person should be designated as responsible for handling complaints and deciding the measures to be taken. This person should have sufficient support staff. If this person is not the Responsible Person, the latter should be made aware of any complaint, investigation or recall.

13.2.3 If a blood or blood component defect or testing error is discovered or suspected, consideration should be given to checking related blood and blood components in order to determine whether they are also affected.

13.2.4 All the decisions and measures taken as a result of a complaint should be recorded. Complaint records should be reviewed regularly for any indication of specific or recurring problems requiring attention and the possible recall of distributed blood and blood components.

13.2. 5 The National regulator should be informed in cases of complaints resulting from possible faulty processing, component deterioration or any other serious quality problems, including the detection of counterfeiting.

13.2.6 There should be a system to ensure effective communication between the blood establishment and the National regulator, so that significant post-donation events may be immediately transmitted to the National regulator. In particular, this procedure should allow early and effective communication of any evidence for the presence of blood-transmissible infection, in a donor whose blood and blood product were transfused.

13.3 Recall

13.3.1 There must be personnel authorized within the blood establishment to assess the need for blood and blood component recalls and to initiate and co-ordinate the necessary actions. An effective recall procedure must be in place, including a description of the responsibilities and actions to be taken. This must include notification of the Competent Authority.

13.3.2 Actions must be taken within pre-defined periods of time and must include tracing all relevant blood components and, where applicable, must include trace-back. The purpose of the investigation is to identify any donor who might have contributed to causing the transfusion reaction and to retrieve available blood components from that donor, as well as to notify consignees and recipients of components collected from the same donor in the event that they might have been put at risk.

13.3.3 Recall operations should be capable of being initiated promptly and at any time. In certain cases, recall operations may need to be initiated to protect public health prior to establishing the root cause(s) and full extent of the quality defect.

13.3.4 The persons authorized to initiate and co-ordinate the recall actions should normally be independent of the commercial management within the organization. If they do not include the executive management and the Responsible Person (blood establishment), the latter should be made aware of any recall operation.

13.3.5 Recalled blood components or products should be identified and stored separately in a secure area while awaiting a decision on their fate. The progress of the recall process should be recorded and a final report issued, including reconciliation of the delivered and recovered quantities of the blood and blood components or products.

The effectiveness of the arrangements for recalls should be regularly evaluated.​

​14.1 General principles

14.1.1 Good documentation constitutes an essential part of the Quality System and is key to operating in compliance with Good Practice requirements. It ensures that work performed is standardized, and that there is a traceability of all steps in the preparation of blood and blood components; i.e., donor selection, collection, processing, testing, storage, dispatch, quality control and quality assurance. Various types of documents and media used should be defined fully in the Quality Management System of the organization.

14.1.2 Documentation may exist in various forms: paper-based, electronic or photographic. The main objective of the system of documentation used should be to establish, control, monitor and record all activities that directly or indirectly impact on all aspects of the quality and safety of blood and blood components as well as any derived medicinal products. The Quality Management System should include sufficient instructional detail to facilitate common understanding of the requirements, in addition to providing for adequate recording of the various processes and evaluation of any observations, so that ongoing application of the requirements may be demonstrated.

14.1.3 There are two primary types of documentation used to manage and record Good Practice compliance: instructions (directions, requirements) and records/reports. Appropriate practices should be applied with respect to the type of document. Suitable controls should be implemented to ensure the accuracy, integrity, availability and legibility of documents. Instruction documents should be free from errors and available in writing. The term ‘written’ means recorded or documented on media from which data may be rendered in a readable form for humans.

14.1.4 Documents setting out specifications, procedures and records covering each activity undertaken by a blood establishment should be in place and kept up-to-date. 

Specifications describe in detail the requirements to which the blood and blood components or materials used or obtained during preparation and distribution must conform. They serve as a basis for quality evaluation. Component monographs in Annex II.

Testing instructions detail all the starting materials, equipment and ised systems (if any) to be used and specify all sampling and testing instructions. If applied, in-process controls should be specified, together with their acceptance criteria. 

 Procedures (otherwise known as Standard Operating Procedures or SOPs) give directions for performing certain operations. 

Protocols give instructions for performing certain discreet operations, and may record the outcome (e.g., qualification and validation protocols).

Technical agreements are agreed between contract givers and acceptors for outsourced activities.

Records should be made or completed at the time each action is taken and in such a way that all significant activities concerning the donation, collection, processing, testing and distribution of blood and blood components are traceable.

14.1.5 The record system must ensure continuous documentation of the procedures performed from the blood donor to the recipient. That is, each significant step must be recorded in a manner that permits a component or procedure to be traced, in either direction, from the first step to final use/disposal.

14.1.6 Any alteration made to the entry on a document should be signed and dated; the alteration should permit reading of the original information. Where appropriate, the reason for the alteration should be recorded.

14.2 Records/Reports

14.2.1 Records provide evidence of various actions taken to demonstrate compliance with instructions, e.g. activities, events, investigations and, in the case of processed blood and blood.

14.2.2 Components, a history of each unit (including its distribution). Records include the raw data that is used to generate other records. For electronic records, regulated users should define which data are to be used as raw data. All data on which quality decisions are based should be defined as ‘raw data’.

14.2.3 Certificates of analysis provide a summary of testing results on samples of reagents, products or materials, together with the evaluation for compliance with a stated specification.

14.2.4 Reports document the carrying out of particular exercises, projects or investigations, together with results, conclusions and recommendations. 

14.3 Generation and control of documentation

14.3.1 All types of documents should be defined and adhered to. Requirements apply equally to all forms of document media types. Complex systems need to be understood, well documented and validated, and adequate controls should be in place. Many documents (instructions and/or records) may exist in hybrid forms (i.e., some elements are electronic and others are paper- based). Relationships and control measures for master documents, official copies, data handling and records need to be stated for both hybrid and homogenous systems.

14.3.2 A document control system, defined in a written procedure, must be established for the review, revision history and archiving of documents, including SOPs. Appropriate controls for electronic documents, such as templates, forms and master documents, should be implemented. Appropriate controls should be in place to ensure the integrity of the record throughout the retention period.

14.3.3 Documents should be designed, prepared, reviewed, and distributed with care. Reproduction of working documents from master documents should not allow errors to be introduced through the reproduction process.

14.3.4 Documents containing instructions should be approved, signed and dated by appropriate and authorized persons. This may also be undertaken electronically. Documents should have unambiguous content and be uniquely identifiable. The effective date should be defined.

14.3.5 Documents containing instructions should be laid out in an orderly fashion and be easy to check. The style and language of documents should fit with their intended use. Standard Operating Procedures, Work Instructions and Methods should be written in an imperative mandatory style. 

14.3.6 Documents within the Quality Management System should be regularly reviewed and kept up-to-date.

14.3.7 All significant changes to documents must be acted upon promptly, and must be reviewed, dated and signed by a person authorized to undertake this task.

14.3.8 Instructional documents should not be hand-written; although, where documents require the entry of data, sufficient space should be provided for such entries.

14.4 Standard Operating Procedures

14.4.1 All activities and critical procedures should be specified in written instructions (SOPs) including but not limited:

        o Donor eligibility

        o Collection and preparation of blood components

        o Laboratory testing, quality control testing

        o Labelling requirements

        o Storage, release, dispatch, transportation

        o Processes of recall of the blood products components

        o Testing materials purchase and receipt

        o Sampling, which include the methods and equipment to be used, the amounts to be taken

        o Quality assurance procedures (complaint investigations, deviation management)

        o Recall of non-conforming products

        o Change control and document control

        o Validation and qualification of processes, equipment and systems; 

        o Equipment calibration; 

        o Maintenance, cleaning and sanitation; 

        o Environmental monitoring; 

        o Investigations of deviations and non-conformances; 

        o Audits of compliance with internal quality/Good Practice; 

        o Summaries of records, where appropriate (e.g., review of the quality of blood components); 

14.4.2 All activities should be carried out according to the standard operating procedures. The standard operating procedures and the processes should be regularly reviewed and updated as necessary in order to improve the quality of products and services delivered. The document review process should itself be documented.

14.5 Retention of documents

14.5.1 It should be clearly defined which record is related to each activity and where this record is located. Secure controls must be in place to ensure the integrity of the record throughout the retention period. These controls must be validated if appropriate. Specific retention requirements for certain documentation apply.

14.5.2 Records must be retained for a period according to local, national Saudi legislation requirements, as appropriate. Traceability data (that allow tracing from donor to recipient and vice versa) should be retained for a minimum of 30 years).

14.5.3 Documentation regarding investigations into Serious Adverse Events and Serious Adverse Reactions should be retained for a minimum of 15 years.

14.5.4 Quality System documentation and associated records should be retained for a minimum of 10 years.

14.5.5 For other types of documentation, the retention period must be defined on the basis of the business activity that the documentation supports. These retention periods should be specified.​

​15.1 Donor eligibility

15.1.1 Procedures for safe identification of donors, suitability interview, and eligibility assessment must be implemented and maintained. They must take place before each donation and comply with the requirements set out.

15.1.2 There must be secure and unique identification, as well as recording of the contact details, of donors. Robust mechanisms must link donors to each of their donations.

15.1.3 Upon arrival at the blood establishment, donors must provide evidence of their identity. All donors must undergo a systematic screening process to assess their suitability.

15.1.4 Only healthy persons with a good medical history can be accepted as donors of blood or blood components.

15.1.5 The selection process must include assessment of each donor carried out by a suitably qualified individual who has been trained to use accepted guidelines and who works under the direction of a physician. 

15.1.6 This assessment involves an interview, a questionnaire and further direct questions, if necessary. Questionnaire must include information that required by national regulations to ensure patient and donor safety and blood / or its components with high quality. 

15.1.7 The donor should be advised before donation of the requirements for blood donors and be informed of the common risks and discomforts associated with donating. 

15.1.8 The donors should be informed about the option to change their mind about donating prior to proceeding further, or the possibility of withdrawing or self-deferring at any time during the donation process, without any undue embarrassment or discomfort. 

15.1.9 Donors should be notified that each donation is tested for the presence of infectious disease markers and be informed of factors that may increase the risk to the recipient of donor blood.

15.1.10 The informed consent form should be given to each donor and it should be signed off by the donor prior to collection. 

15.1.11 The questionnaire must be designed to elicit information relevant to the health and lifestyle of the donor. It must be designed to be understandable by the donor and given to all donors each time they attend. On completion, it must be signed by the donor.

15.1.12 Relevant acceptance/deferral criteria must be in place at the blood establishment to control acceptance and deferral of donors.

15.1.13 The minimal criteria for donor selection should include essential indicators, as: 

           • The limits on the age of the donor; 

           • The maximum volume collected at one donation; 

           • The critical time intervals between donations; 

           • The extent of the medical assessment; 

           • The evaluation of the medical history, including history of infectious diseases (including regional epidemiology); 

           • The factors in history and behavior which may increase infection risk; 

           • The reason for temporary deferral, including the length of time before donor acceptance is agreed; 

           • The reason for permanent exclusion from further donation; 

           • The type of medication being used. 

           • The criteria for an apheresis donor should meet at least the general acceptance criteria for blood donation, unless otherwise specified. 

15.1.14 The donor interview must be conducted in such a way as to ensure confidentiality. The confidential interview must be conducted by specifically-trained staff to ask further direct questions to supplement the information in the questionnaire. The person who carries out the assessment must certify that the relevant questions have been asked.

15.1.15 Records of suitability and final assessment of donors must be signed by a qualified healthcare professional. Records should be kept for each activity associated with the selection of the donor. The record should reflect the decision to accept the donor by taking into consideration the medical history, history of deferral, donor interview, and results of the physical examination. Rejection of a donor and the reason for deferral should be recorded. A system must be in place to ensure that the donor is prevented from making future donations during a permanent or temporary legal period (including for the duration of a temporary deferral).

15.1.16 Donors must be instructed to inform the blood establishment if signs or symptoms occur after a donation. This scenario indicates that the donation may have been infectious or that any other information not disclosed during the health screening may render prior donation unsuitable for transfusion.

15.1.17 Procedures must be in place to ensure that any abnormal findings arising from the donor selection process are properly reviewed by a qualified health professional and that appropriate action is taken.

15.2 Collection of blood and blood components

15.2.1 The procedure for blood collection must be designed to ensure that the identity of the donor is verified and recorded securely, and that the link between the donor and blood, blood components and blood samples is established clearly

15.2.2 Donor identity must be confirmed before each critical step in the process but, at the very least, before donor selection and venipuncture.

15.2.3 A system of unique donation numbers should be used to identify each donor and the related donation and all of its associated components, samples and records, as well as to link each one to each of the others.

15.2.4 During or following the donation, all records, blood bags and laboratory samples should be checked for the issued donation number. Donation number labels that have not been used should be discarded using a controlled procedure.

15.2.5 Systems of sterile blood bags used for the collection of blood and blood components and their processing must be SFDA approved or comply with equivalent standards if the blood and blood components are collected in third countries. The batch number of the bag must be traceable for each blood component.

15.2.6 All handling of materials and reagents, such as receipt and quarantine, sampling, storage, labelling, processing, packaging and distribution, should be done in accordance with written procedures or instructions and, if necessary, recorded.

15.2.7 Only reagents and materials from approved suppliers that meet documented requirements and specifications should be used.

15.2.8 Blood collection procedures must minimize the risk of microbial contamination. Sterile collection and processing systems for blood should be used for blood and blood components. Collection systems should be used in accordance with manufacturer instructions.

15.2.9 Before venipuncture, a check should be made to ensure that the collection system to be used is not damaged or contaminated, and that it is appropriate for the intended collection. Abnormal moisture or discoloration could suggest a defect.

15.2.10 Appropriate procedures for hand disinfection and personal hygiene should be in place, and should be performed by personnel before each donation.

15.2.11 The skin at the venipuncture site must be free from lesions, including eczema.

15.2.12 The venipuncture site must be prepared using a defined and validated disinfection procedure. The antiseptic solution must be allowed to dry completely before venipuncture. The prepared area must not be touched with fingers before needle insertion.

15.2.13The effectiveness of the disinfection procedure must be monitored and corrective action taken where it is indicated to be defective. The expiry date of the disinfectant should be checked. The date of manufacture and the date of opening of in-house disinfectants should be stated on their labels.

15.2.14 The blood container must be checked after donation for any defect. The integral blood bag collection tubing should be sealed off at the end as close as possible to the blood bag.

15.2.15 The blood flow should not be interrupted for a significant time period during blood collection. The maximum collection time to accept the donation for component preparation should be specified and controlled. Donations which exceed the maximum time period should be recorded and not be used for component preparation. 

15.2.16 The blood bag should be checked after donation for any defect. 

15.2.17 Standard Operating Procedures should be in place describing the actions to be taken following an unsuccessful donation. It should specify how to handle already labelled material and the circumstances under which a repeat venipuncture might be possible. 

15.2.18 Laboratory samples must be taken at the time of donation and be appropriately stored prior to testing.

15.2.19 The procedure used for the labelling of records, blood bags, and laboratory samples with donation numbers must be designed to avoid any risk of identification error and mix-up.

15.2.20 After blood collection, blood bags must be handled in a way that maintains the quality of the blood and at a storage temperature and transport temperature appropriate to the requirements for further processing.

15.2.21 Blood and blood components should be placed in controlled and validated conditions as soon as possible after venipuncture. Donations and samples should be transported to the processing site in accordance with procedures that ensure a constant approved temperature and secure confinement. There should be validation data to demonstrate that the method of transport maintains the blood within the specified temperature range throughout the period of transportation. Alternatively, portable temperature loggers may be used to record the temperature during transportation of blood to the processing site.

15.2.22 If a deviation occurs, it should be approved in writing by a competent person.

15.2.23 Where the blood is not transported by the processing establishment itself, the responsibilities of the transport company should be clearly defined and periodic audits should be conducted to ensure compliance.

15.2.24 There must be a system in place to ensure that each donation can be linked to the collection and processing system into which it was collected and/or processed.

15.3 Blood testing

15.3.1 All blood donations should be tested to ensure that they meet specifications and to ensure a high level of safety to the recipient.

15.3.2 Any laboratories doing mandatory donor screening tests for blood shall be licensed for those tests by the SFDA.

15.3.3 In addition to the validation of the test system by the manufacturer, an on-site validation of the test system in the laboratory is required prior to its use in routine testing. This validation should demonstrate that:

           o The performance specifications of the system established by the kit manufacturer are met by the laboratory;

           o Laboratory personnel are thoroughly instructed, trained and competent to operate the test system.

15.3.4 All donation testing activities, handling of donor specimens, sampling, analysis and data processing should be undertaken independently of diagnostic testing of patients.

15.3.5 Each step of the handling and processing of samples should be described and appropriately documented, as should the conditions of pre-analytical treatment of specimens (e.g. centrifugation), storage and transportation (duration, temperature, type of container, storage after testing).

15.3.6 Upon receipt of samples at the laboratory, positive identification of the samples received against those expected should be carried out.

15.3.7 There must be data confirming the suitability of any laboratory reagents used in testing of donor samples and blood-component samples.

15.3.8 Testing of blood components should be carried out in accordance with the recommendations of the manufacturer of reagents and test kits (unless an alternative method has been validated before their use) before release of the blood component.

15.3.9 Pre-acceptance testing must be performed on samples before purchasing batches of commercial reagents. Prospective purchasers must require potential suppliers to provide them with full validation data for all lots of reagents. Each lot of reagent must be qualified by the purchaser to demonstrate suitability for its intended purpose within the system used for testing.

15.3.10 There must be a reliable process in place for transcribing, collating and interpreting results. 

15.3.11 The quality of the laboratory testing must be assessed regularly by participation in a formal system of proficiency testing, such as an external quality assurance programme.

15.4 Testing for infectious markers

15.4.1 Testing of donations for infectious agents is a key factor in ensuring that the risk of disease transmission is minimized and that blood components are suitable for their intended purpose.

15.4.2 Each donation must be tested in conformity with the requirements laid down in Annex I.

15.4.3 Additional testing for other agents or markers may be required, taking into account the epidemiological situation in any given region or country.

15.4.4 Serological testing should be performed on samples transferred directly into the analyzer from the original sample tube. Secondary aliquot samples may be used for NAT testing of mini- pools of individual samples.

15.4.5 If NAT testing is performed by assembling various samples in mini-pools, a thoroughly validated system of labelling/identification of samples, a validated strategy and pooling process, and a validated algorithm to re-assign pool results to individual donations should be in place.

15.4.6 There must be clearly defined procedures to resolve discrepant results. 

15.4.7 Blood and blood components that have a repeatedly reactive result in a serological screening test for infection with the viruses mentioned in Annex I must be excluded from therapeutic use and must be stored separately in a dedicated environment. Appropriate confirmatory testing must take place. In the case of confirmed positive results, appropriate donor management must take place, including the provision of information to the donor and follow-up procedures.

15.4.8 Screening algorithms should be defined precisely in writing (i.e., Standard Operating Procedures) to deal with initially reactive specimens, and to resolve discrepancies in results after re-testing.

15.4.9 The testing requirements in the Kingdom of Saudi Arabia include Anti-HIV I and II and NAT for HIV, Hepatitis B surface Antigen and NAT for Hepatitis B, Anti Hepatitis C, Anti HTLV I and II and NAT for Hepatitis C, Syphilis and Malaria. The testing reagents (including methodology) must be approved and authorized by SFDA.

15.4.10 The time period between the donation date and the availability of the test results for viral marker testing should be defined and kept as short as possible. The turnaround times should be monitored as part of the trending process to assess the performance of the laboratory.

15.5 Blood group serological testing of donors and donations

15.5.1. Blood group serology testing must include written procedures for testing specific groups of donors (e.g., first-time donors, donors with a history of transfusion).

15.5.2 Each donation should be tested for ABO and RhD blood groups and at least all first-time donors should be tested for clinically-significant irregular red-cell antibodies.

15.5.3 ABO and RhD blood groups should be verified on each subsequent donation.

15.5.4 Comparison should be made with the historically determined blood group. If a discrepancy is found, the applicable blood components should not be released until the discrepancy has been resolved unequivocally.

15.5.5 Donors with a history of transfusions or pregnancy since their last donation should be tested for clinically-significant irregular red-cell antibodies. If clinically significant red-cell antibodies are detected and, if applicable, the blood or blood component should be labelled accordingly.

15.5.6 Only test reagents that have been licensed or evaluated and considered to be suitable by SFDA must be used.

15.5.7 The manufacturer of critical reagents as Blood Grouping and testing for infectious diseases reagents must have a full Quality System certified by a notified body, and must submit an application containing all the control results for each lot.

15.5.8 Quality-control procedures must be implemented for the equipment, reagents and techniques used for ABO and RhD blood grouping and phenotyping as well as detection and identification of Allo-antibodies. The frequency of the control is dependent on the method used.​

​Component Monographs (EDQM Guide to the preparation, use and quality assurance of Blood Components 19th Edition)

Whole Blood

Definition: Whole blood is blood taken from a suitable donor following the appropriate procedures and in the appropriate container to be transfused either without further processing or as source material for further processing.
​

Parameter to be checked - Requirements                                          Frequency of control

ABO, RhD Grouping                                                                                 All units

Anti-HIV 1 & 2 Negative by approved screening test                        All units

HBsAg Negative by approved screening test                                     All units

Anti-HCV Negative by approved screening test                                All units

Malaria Negative        by approved screening test                            All units

Syphilis Negative       by approved screening test                            All Units

Hepatitis B NAT           Negative                                                            All units

HIV by NAT                 Negative                                                              All units

Hepatitis C by NAT      Negative                                                           All units

Anti-HTLV I and II      Negative                                                             All units

Volume             450mls+/- 50mls (excluding anti-coagulant)  1% of units Minimum of 4        units/month

When 300 to 404 mL of whole blood is collected into an anticoagulant volume calculated for  450 ± 45 mL

or when 333 to 449 mL of whole blood is collected into an anticoagulant  volume calculated for 500 ± 50 mL;

Red cells prepared from the resulting unit shall be labeled Red Blood Cells Low Volume. No other components shall be made from a low volume collection.

Hemoglobin Minimum 45g/unit                                     4units/month

Hemolysis at end of storage                                           4 units /month

Whole Blood Leukocytes Reduced                                95% of units contain <5 ×10*6 leukocytes

Storage and transport

Red Cells, must be kept at a controlled temperature between

+ 2 and + 6 °C during storage. Depending on the anticoagulant/additive system, the storage time depends on the anticoagulant used.

Validated transport systems must ensure that at no time during a maximum transit time of 24 hours did the temperature exceed + 10 °C.

Whole blood for processing into components may be kept up to 24 hours in conditions validated to maintain a temperature between +20 C and 24 C which is required for the preparation of platelets from whole blood.

Red Cells Leucocyte depleted in additive solution

Definition: This is the red cell fraction from whole blood and removing the majority of leucocytes by leucocyte filtration and suspended in additive solution.

Parameter to be checked - Requirements                                          Frequency of control

ABO, RhD Grouping                                                                                 All units

Anti-HIV 1 & 2 Negative by approved screening test                       All units HBsAg Negative        by approved screening test                                         All units

Anti-HCV Negative   by approved screening test                              All units

Malaria Negative        by approved screening test                           All units

Syphilis Negative       by approved screening test                           All units

Hepatitis B NAT        Negative                                                              All units

HIV by NAT              Negative                                                                All units

Hepatitis C by NAT   Negative                                                             All units

Anti-HTLV I and II   Negative                                                              All units

Volume a to be defined for the system used                                                   as determined by SPC

Hematocrit 50 % - 70 %                                                                                      as determined by SPC

Hemoglobin a Minimum 40 g per unit                                                             as determined by SPC

Residual leucocyte content a < 1 × 106 per unit                                           as determined by SPC

Hemolysis at the end of storage a < 0.8 % of red cell mass                       as determined by SPC A minimum of 90 % of units tested should meet the required value.

Storage and transport

Red Cells, must be kept at a controlled temperature between + 2 and + 6 °C during storage. Depending on the anticoagulant/additive system, the storage time may be extended up to the approved limit of the additive solution system.

Validated transport systems must ensure that at no time during a maximum transit time of 24 hours did the temperature exceed + 10 °C.

Red Cells (Irradiated)

Definition: The red cell component is irradiated either by gamma or Xray irradiation.

The irradiation must ensure that all the product will receive a dose of between 25 and 50 Gray. Regular dose mapping must be undertaken.

The same parameters as for the particular red cell component are to be followed.

Storage and transport

Red cells may be irradiated up to 28 days after collection. Post irradiation they should be used as soon as possible but never more than 14 days post irradiation or within a maximum of 28 days post collection.

Red Cells, must be kept at a controlled temperature between + 2 and + 6 °C during storage.

Validated transport systems must ensure that at no time during a maximum transit time of 24 hours did the temperature exceed + 10 °C.

Platelets (Recovered: Pooled)

Definition: This is the pooled platelet component from a number of whole blood units suspended in plasma.

Parameter to be checked - Requirements                                         Frequency of control

ABO, RhD Grouping                                                                               All units

Anti-HIV 1 & 2 Negative by approved screening test                      All units

HBsAg Negative by approved screening test                                   All units

Anti-HCV Negative by approved screening test                               All units

Malaria Negative         by approved screening test                         All units

Syphilis Negative        by approved screening test                         All Units

Hepatitis B NAT         Negative                                                           All units

HIV by NAT               Negative                                                              All units

Hepatitis C by NAT    Negative                                                           All units

Anti-HTLV I and II    Negative                                                            All units

Platelet content per final unit a > 3 × 1011                                        as determined by SPC

Residual leucocyte content b < 5 × 106   per unit                             as determined by SPC PH measured (+22°C)

at the end of the recommended shelf-life > 6.4                                as determined by SPC

1. A minimum of 90 % of units tested should meet the required value.

2. These requirements are deemed to have been met if 90 % of the tested units fall within the values indicated.

3. All tested units must comply. Measurement of the pH in a closed system is preferable to prevent CO2 escape.

Measurement may be made at another temperature and then corrected.

Storage and transport

The storage temperature must be between + 20 to + 24 °C, under constant agitation.

The maximum storage time for Platelets, may be extended to 7 days depending on the type of additive solution and following appropriate validation.

Platelets, Recovered, Pooled, Leucocyte-Depleted

Definition: This is the pooled platelet component from a number of whole blood units suspended in plasma and the leucocyte content significantly reduced by filtration.

Parameter to be checked - Requirements                                       Frequency of control

ABO, RhD Grouping                                                                              All units

Anti-HIV 1 & 2 Negative by approved screening test                     All units

HBsAg Negative by approved screening test                                  All units

Anti-HCV Negative by approved screening test                              All units

Malaria Negative        by approved screening test                         All units

Syphilis Negative       by approved screening test                          All Units

Hepatitis B NAT        Negative                                                            All units

HIV by NAT              Negative                                                              All units

Hepatitis C by NAT   Negative                                                           All units

Platelet content per final unit a > 5.5 × 1010                                    as determined by SPC

Residual leucocytes per final unit a < 8.3 × 105                               as determined by SPC pH measured (+ 22 °C)

at the end of the recommended shelf-life b> 6.4                              as determined by SPC a A minimum of 90 % of units tested should meet the required value.

b All tested units must comply. Measurement of the pH in a closed system is preferable to prevent CO2 escape.

Measurement may be made at another temperature and then corrected.

Storage and transport

The storage temperature must be between + 20 to + 24 °C, under constant agitation.

The maximum storage time for Platelets, may be extended to 7 days depending on the type of additive solution and following appropriate validation.

Platelet (Apheresis)

Definition: This is the component from whole blood obtained by apheresis from a single donor using an apheresis equipment.

Parameter to be checked - Requirements                                          Frequency of control

ABO, RhD Grouping                                                                                All units

Anti-HIV 1 & 2 Negative by approved screening test                       All units

HBsAg Negative by approved screening test                                    All units

Anti-HCV Negative by approved screening test                                All units

Malaria Negative        by approved screening test                           All units

Syphilis Negative       by approved screening test                           All Units

Hepatitis B NAT        Negative                                                              All units

HIV by NAT              Negative                                                                All units

Hepatitis C by NAT   Negative                                                               All units

Platelet content a Standard unit: minimum 3 × 1011 per unit    as determined by SPC Residual leucocyte content b < 5 × 106 per unit                                             as determined by SPC

pH measured (+ 22 °C)

at the end of the recommended shelf-life c> 6.4                              as determined by SPC

 a     A minimum of 90 % of units tested should meet the required value.

b      These requirements are deemed to have been met if 90 % of the tested units fall within the values indicated.

c     Measurement of the pH in a closed system is preferable to prevent CO2 escape. Measurement may be made at another temperature and then corrected.

Storage and transport

The storage temperature must be between + 20 to + 24 °C, under constant agitation.

The maximum storage time for Platelets, may be extended to 7 days depending on the type of additive solution and following appropriate validation.

Fresh Frozen Plasma

Definition: This is the liquid part from whole blood which may be used for transfusion or for further processing and fractionation. It may be obtained from whole blood or apheresis.

Parameter to be checked - Requirements                                           Frequency of control

ABO, RhD a, b Grouping only for clinical FFP                                      All units

Anti-HIV 1 & 2 a Negative by approved screening test                     All units

HbsAg a Negative by approved screening test                                  All units

Anti-HCV a Negative by approved screening test                             All units

Malaria Negative        by approved screening test                            All units

Syphilis Negative       by approved screening test                            All units

Factor VIII b Average (after freezing and thawing): not less than 700 IU/L.

Residual cells b Red cells: < 6.0 × 109/L

Leucocytes: < 0.1 × 109/L                                                                as determined by SPC

Platelets: < 50 × 109/L                                                                      as determined by SPC

If leucocyte-depleted:< 1 × 106 per unit                                          as determined by SPC

Leakage: No leakage in any part of container.

Requires visual inspection after pressure in a plasma

extractor before freezing.                                                                  All units

Visual changes no abnormal color or visible clots                           All units

a.   Unless performed on the source whole blood.

b.   A minimum of 90 % of units tested should meet the required value.

Storage:

The following storage times and temperatures are permitted:

• -        –18 C or below: 12 months from collection.

Cryoprecipitate

Definition: This is a product from further processing of fresh frozen plasma. It contains Factor VIII, VWf, Fibrinogen, Factor XIII and Fibronectin

Parameter to be checked - Requirements                                          Frequency of control

ABO, RhD Grouping                                                                                 All units

Anti-HIV 1 & 2 Negative by approved screening test                        All units

HBsAg Negative by approved screening test                                    All units

Anti-HCV Negative by approved screening test                               All units

Malaria Negative        by approved screening test                           All units

Syphilis Negative       by approved screening test                           All Units

Hepatitis B NAT        Negative                                                              All units

HIV by NAT              Negative                                                               All units

Hepatitis C by NAT   Negative                                                            All units

Anti-HTLV I and II   Negative                                                             All units

 Volume (if from whole blood) 30 to 40 mls                                   All units

Factor VIII     > 80 IU/unit                        1 % of all units, minimum 4 /months

Fibrinogen       > 150  

vWf                 > 100IU/unit

Storage:

The following storage times and temperatures are permitted:

-         –18 C or below: 12 months from collection

​

     (European) Commision Directives 2002/98/EC

     2004/33/EC

      2005/61/EC

     2005/62/EC

     2016/1214

    Pic/S Aide Memoire to Inspections of Blood Establishments (Incl. Hospital Blood Banks) And Plasma Warehouses (2021)

     Guide to the preparation, use and quality assurance of Blood Components (EDQM 19th Edition)